Autoimmune enteropathy is a life-threatening disorder of infancy that almost exclusively affects males. It is characterized by intractable diarrhea and a constellation of associated autoimmune diseases, including membranous glomerulonephritis, insulin-dependent diabetes, hemolytic or sideroblastic anemia, autoimmune hepatitis, sclerosing cholangitis, and hypothyroidism (553). Infants present with unexplained episodes of protracted diarrhea and no response to dietary therapy. The disease can also occur in adults (553).

Infants with autoimmune enteropathy demonstrate circulating antienterocyte antibodies (554). The autoantigen is a 75-kD protein encoded on chromosome 19p13, with homology to the tumor suppressor gene MCC. It has therefore been named MCC2 (555). A subset of patients suffers from the systemic familial syndrome of autoimmunity: IPEX (immune dysregulation, polyendocrinopathy, and X-linkage) syndrome. This syndrome is also referred to as XLAD (X-linked autoimmunity and allergic dysregulation) (556). All patients with this syndrome develop autoimmune enteropathy. The IPEX syndrome results from germline mutations in the FOXP3 gene on the X chromosome (557). FOXP3 controls the development of regulatory CD4+ CD25+ T cells that are essential for maintenance of tolerance to self-tissues. The small intestinal lamina propria normally contains a CD25+ FOXP3+ CD4+ cells (558).